Genome-wide DNA methylation investigation of glucocorticoid exposure within buccal samples.

AIM: Glucocorticoids play a major role in regulating the stress response, and an imbalance of glucocorticoids has been implicated in stress-related disorders. Within mouse models, CpGs across the genome have been shown to be differentially methylated in response to glucocorticoid treatment, and using the Infinium 27K array, it was shown that humans given synthetic glucocorticoids had DNA methylation (DNAm) changes in blood. However, further investigation of the extent to which glucocorticoids affect DNAm across a larger proportion of the genome is needed. METHODS: Buccal samples were collected before and after synthetic glucocorticoid treatment in the context of a dental procedure. This included 30 tooth extraction surgery patients who received 10 mg of dexamethasone. Genome-wide DNAm was assessed with the Infinium HumanMethylationEPIC array. RESULTS: Five CpGs showed genome-wide significant DNAm changes that were >10%. These differentially methylated CpGs were in or nearest the following genes: ZNF438, KLHDC10, miR-544 or CRABP1, DPH5, and WDFY2. Using previously published datasets of human blood gene expression changes following dexamethasone exposure, a significant proportion of genes with false-discovery-rate-adjusted significant CpGs were also differentially expressed. A pathway analysis of the genes with false-discovery-rate-adjusted significant CpGs revealed significant enrichment of olfactory transduction, pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and steroid hormone biosynthesis pathways. CONCLUSION: High-dose synthetic glucocorticoid administration in the setting of a dental procedure was significantly associated with DNAm changes within buccal samples. These findings are consistent with prior findings of an influence of glucocorticoids on DNAm in humans.

Delirium detection by a novel bispectral electroencephalography device in general hospital.

AIM: Delirium is common and dangerous among elderly inpatients; yet, it is underdiagnosed and thus undertreated. This study aimed to test the diagnostic characteristics of a noninvasive point-of-care device with two-channel (bispectral) electroencephalography (EEG) for the screening of delirium in the hospital. METHODS: Patients admitted to the University of Iowa Hospitals and Clinics were assessed for the presence of delirium with a clinical assessment, the Confusion Assessment Method for Intensive Care Unit and Delirium Rating Scale. Subsequently, we obtained a 10-min bispectral EEG (BSEEG) recording from a hand-held electroencephalogram device during hospitalization. We performed power spectral density analysis to differentiate between those patients with and without delirium. RESULTS: Initially 45 subjects were used as a test dataset to establish a cut-off. The BSEEG index was determined to be a significant indicator of delirium, with sensitivity 80% and specificity 87.7%. An additional independent validation dataset with 24 patients confirmed the validity of the approach, with a sensitivity of 83.3% and specificity of 83.3%. CONCLUSION: In this pilot study, the BSEEG method was able to distinguish delirious patients from non-delirious patients. Our data showed the feasibility of this technology for mass screening of delirium in the hospital.

Rate of recurrent anaphylaxis and associated risk factors among Olmsted County, Minnesota, residents: A population-based study.

BACKGROUND: The rate and risk factors for recurrence of anaphylaxis are not well known. OBJECTIVE: To measure the rate and risk factors for recurrent anaphylaxis in a population-based cohort in Olmsted County, Minnesota. METHODS: We conducted a population-based cohort study using the Rochester Epidemiology Project, a comprehensive medical records linkage system, to obtain records of patients who presented to medical centers within the Olmsted County area with anaphylaxis from January 1, 2001, through December 31, 2010. We evaluated the rate and associations of risk factors with anaphylaxis recurrence. RESULTS: Among the 611 patients with anaphylaxis, 50 (8%) experienced a total of 60 recurrences within the 10-year period, resulting in a recurrence rate of 2.6 per 100 person-years. A history of atopic dermatitis (hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.0-16.1; P = .001), presenting symptoms of cough (HR, 4.7; 95% CI, 2.1-10.7; P < .001) oral pruritus (HR, 9.9; 95% CI, 4.3-23.2; P < .001), and receiving corticosteroids (HR, 5.2; 95% CI, 2.3-11.7; P < .001) were associated with an increased risk of recurrence. The cardiovascular symptom of chest pain (HR, 0.24; 95% CI, 0.07-0.79; P = .02) was associated with a decreased risk of recurrence. CONCLUSION: In this epidemiologic study, the rate of recurrence was 8% during the 10-year study period (recurrence rate of 2.6 per 100 person-years). Those with atopic dermatitis and mucocutaneous or respiratory symptoms were more likely to have a recurrent anaphylactic event. Our findings underscore the importance of early patient access to self-injectable epinephrine and referral to an allergist/immunologist for additional testing and education.

Identification of Patients With High Mortality Risk and Prediction of Outcomes in Delirium by Bispectral EEG.

BACKGROUND: Delirium is common and dangerous, yet underdetected and undertreated. Current screening questionnaires are subjective and ineffectively implemented in busy hospital workflows. Electroencephalography (EEG) can objectively detect the diffuse slowing characteristic of delirium, but it is not suitable for high-throughput screening due to size, cost, and the expertise required for lead placement and interpretation. This study hypothesized that an efficient and reliable point-of-care EEG device for high-throughput screening could be developed. METHODS: This prospective study, which measured bispectral EEG (BSEEG) from elderly inpatients to assess their outcomes, was conducted at the University of Iowa Hospitals and Clinics from January 2016 to October 2017. A BSEEG score was defined based on the distribution of 2,938 EEG recordings from the 428 subjects who were assessed for delirium; primary outcomes measured were hospital length of stay, discharge disposition, and mortality. RESULTS: A total of 274 patients had BSEEG score data available for analysis. Delirium and BSEEG score had a significant association (P < .001). Higher BSEEG scores were significantly correlated with length of stay (P < .001 unadjusted, P = .001 adjusted for age, sex, and Charlson Comorbidity Index [CCI] score) as well as with discharge not to home (P < .01). Hazard ratio for survival controlling for age, sex, CCI score, and delirium status was 1.35 (95% CI,1.04 to 1.76; P = .025). CONCLUSIONS: In BSEEG, an efficient and reliable device that provides an objective measurement of delirium status was developed. The BSEEG score is significantly associated with pertinent clinical outcomes of mortality, hospital length of stay, and discharge disposition. The BSEEG score better predicts mortality than does clinical delirium status. This study identified a previously unrecognized subpopulation of patients without clinical features of delirium who are at increased mortality risk.

Turning Points in the Lives of Youth of With/Without ADHD: Are They Linked to Changes in Substance Use?

OBJECTIVE: This study examines the behavior beliefs, social supports, and turning points in individuals with/without ADHD related to their substance use/abuse (SU/A) decisions. METHOD: The coded interviews from 60 participants with/without ADHD were compared for their SU/A decisions and precipitants with these decisions among abstainers, persisters, and desisters. RESULTS: ADHD participants reported fewer social advantages to avoid SU/A than non-ADHD participants. Desisters and persisters reported more social advantages of using drugs than abstainers. Persisters reported both more negative and positive psychological/physiological effects of SU/A. ADHD participants reported fewer positive role models in their lives. Non-ADHD patients reported more positive turning points than ADHD participants, regardless of SU/A status. CONCLUSION: ADHD individuals face challenges in making healthy decisions about SU/A due to lack of positive role models. Reinforcing accurate behavioral beliefs may be important to change behaviors in individuals with SU/A or to prevent SU/A initiation in ADHD individuals.

How does a real-world child psychiatric clinic diagnose and treat attention deficit hyperactivity disorder?

AIM: To investigate child and adolescent psychiatrists' (CAPs) attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) diagnoses and treatments in real-world clinical practice. METHODS: The medical records of 69 ADHD children (mean age = 9.5 years), newly referred to the ADHD clinic, were reviewed for their scores of parent- and teacher-reported Vanderbilt ADHD Diagnostic Rating Scales (VADRSs), CAPs' diagnoses of ADHD and ODD, and CAPs' treatment recommendations. Among 63 ADHD subjects who completed both parent and teacher VADRSs, we examined the agreement of the parent and teacher VADRSs. We also examined the concurrent validity of CAPs' ODD diagnoses against the results from the VADRSs. In addition, we compared CAPs' treatment recommendations against established ADHD and ODD guidelines. RESULTS: Among 63 ADHD subjects, the majority of the subjects (92%) met full ADHD diagnostic criteria at least in one setting (parent or teacher) on the VADRSs. Nearly half of the patients met full ADHD diagnostic criteria in two settings (parent and teacher). Relatively low agreement between the parent and teacher VADRSs were found (95%CI: -0.33 to 0.14). For 29 children who scored positive for ODD on the rating scales, CAPs confirmed the ODD diagnosis in only 12 of these case-positives, which is considered as a fair agreement between CAPs and VADRSs (95%CI: 0.10-0.53). For 27 children with no ODD diagnosis made by either CAP or VADRS, more than half of them were recommended for medication only. In contrast, where CAPs made the diagnosis of ODD, or where the parent or teacher VADRS was positive for ODD, almost all of the patients received recommendations for medication and behavior therapy. CONCLUSION: CAPs' ADHD diagnoses have strong concurrent validity against valid rating scales, but ADHD's most common comorbid condition - ODD - may be under-recognized.